This application claims priority under 35 U.S.C. xc2xa7119 OF FR-98/09509, filed Jul. 24, 1998, assigned to the assignee hereof and hereby expressly incorporated by reference.
1. Technical Field of the Invention
The present invention relates to novel 2-amino-4-alkylaminopyrimidine 3-oxide chemical compounds, to compositions comprised thereof and to the use of such novel compounds/compositions as active principles for inducing and/or stimulating hair growth and/or for preventing hair loss.
2. Description of the Prior Art
In human subjects the growth and renewal of the hair are principally determined by the activity of the hair follicles. This activity is cyclic and essentially entails three phases, i.e., the anagenic phase, the catagenic phase and the telogenic phase.
The active anergenic phase, or growth phase, which lasts for several years and during which the hair elongates, is followed by a very short and transient catagenic phase which lasts for a few weeks, and then a rest or quiescent phase, designated the telogenic phase, which lasts for a few months.
At the end of the rest period, the hair falls out and another cycle begins anew. The head of hair is thus under constant renewal, and out of the approximately 150,000 hairs on a head of hair, at any given instant approximately 10% are at rest and will thus be replaced within a few months.
However, different causes can lead to a considerable, temporary or permanent, loss of hair. Alopecia is essentially due to a disruption in hair renewal which occasions, in a first stage, an acceleration of the frequency of the cycles, at the expense of the quality of the hair and then at the expense of its quantity. A gradual depletion of the head of hair takes place by regression of the so-called xe2x80x9cterminalxe2x80x9d hairs at the downy stage. Certain regions are preferentially affected, in particular the temples or frontal bulbs in men, and in women, diffuse alopecia of the vertex is observed.
By the term xe2x80x9calopeciaxe2x80x9d are intended the entire family of afflictions of the hair follicle, the final consequence of which is the partial or general permanent loss of the hair. In a large number of cases, early loss of the hair arises in genetically predisposed individuals and especially affects men. This more particularly applies to androgenetic or androgenic or even androgeno-genetic alopecia.
Active substrates for suppressing or reducing alopecia, and in particular for inducing or stimulating hair growth or reducing hair loss, have long been considered desiderata in the cosmetics and pharmaceutical industries.
In this respect, a large number of very diverse active compounds have already been suggested for such purposes, for example, 2,4-diamino-6-piperidino-pyrimidine 3-oxide or xe2x80x9cMinoxidilxe2x80x9d described in U.S. Pat. Nos. 4,139,619 and 4,596,812, or the many derivatives thereof, such as those described, for example, in EP-0,353,123, EP-0,356,271, EP-0,408,442, EP-0,522,964, EP-0,420,707, EP-0,459,890 and EP-0,519,819.
Nonetheless, serious need continues to exist for yet other active agents/species potentially more active and/or less toxic than those active substrates to date characterizing the state of this art.
Accordingly, a major object of the present invention is the provision of novel 2-amino-4-alkylaminopyrimidine 3-oxide compounds having the structural formula (I): 
in which R1 is an alkyl radical having from 5 to 20 carbon atoms, and Z is either a hydrogen atom or a radical xe2x88x92OR2, wherein R2 is an alkyl radical having from 1 to 12 carbon atoms, as well as the acyl derivatives or acid addition salts thereof.
The subject compounds are well suited as active principles for inducing and/or stimulating hair growth and/or preventing hair loss.
More particularly according to the present invention, it is known to this art that certain polyunsaturated fatty acids, in particular those having 20 carbon atoms, such as arachidonic acid, dihomo-xcex3-linolenic acid and eicosapentaenoic acid, can be converted in vivo, under the influence of certain specific enzymes contained in living cells, in particular epithelial cells, into certain yet other compounds of eicosanoid type which are useful to the body.
Thus, it is known to this art that the enzymes designated cyclooxygenated generate, from the different fatty acids indicated above, particularly from arachidonic acid, eicosanoids of prostaglandin and thromboxane type, and that the enzymes deemed lipoxygenases are responsible for the formation of eicosanoids of leukotriene type and other hydroxylated acyclic acids containing 20 carbon atoms. Depending on the nature of the enzyme with which it reacts first, the same given polyunsaturated fatty acid (or substrate) may be responsible for the formation of several different metabolites, namely, for example, prostaglandins and leukotrienes.
Cyclooxygenase activity can be defined as the enzymatic activity which converts certain polyunsaturated fatty acids into cyclized oxygenated compounds which are, indeed, highly unstable endoperoxides which thereafter enter the subsequent metabolic pathways.
Prostaglandin-endoperoxide synthase, or cyclooxygenase (or PGHS, EC 1.14.99.1), which is a haemoprotein, is an example of these enzymes exhibiting such activity. It is involved in one of the metabolic pathways of prostaglandins.
It too is known that the enzymatic transformations indicated above and the various reaction products resulting therefrom exert an appreciable influence on the mechanisms of growth of body and/or head hair.
In this respect, it has now been shown that by promoting one or other of the two enzymatic pathways, cyclooxygenated or lipoxygenated, in skin and/or scalp cells, it is possible to substantially modify the growth of body and/or head hair. Compare EP-94/402,055, assigned to the assignee hereof.
Essentially, in the aforesaid patent application, promoting one of the pathways over the other is described, by the administration of a combination of compounds combining an inhibitor of one of the pathways with a stimulator of the other pathway.
Even more specifically, it has now been shown that the growth of body and/or head hair can be promoted and/or their loss can be controlled by promoting the cyclooxygenase pathway, for example by activating PGHS and inhibiting the lipoxygenase pathway.
The involvement of these enzymes in several metabolic pathways and the consequences which may ensue from deregulating their functioning are such that extensive research has been undertaken in order to develop active agents with the capacity either of increasing or of reducing the activity of these enzymes.
Arachidonic acid metabolites, nitrogen monoxide and nitrogen-monoxide-donating compounds, stanozolol, glutathione-donating compounds, calcium ionophores, anthocyanosides, bioflavonoids, platelet activating factors (PAF), pro-inflammatory cytokines agents and bacterial endotoxins are recognized, in particular, in the field of cyclooxygenase activators.
Similarly, illustrative is 6-chloro-2,3-dihydroxy-1,4-naphthoquinone (CNDQ), which has the particular feature of being both a lipoxygenase inhibitor and a cyclooxygenase stimulator (C. J. Bedord et al., The Journal of Investigative Dermatology, 81:566-571 (1983)).
However, most of these species present the major drawback of having a broad functional spectrum, which entails that, in general, they have no genuine specificity for cyclooxygenase. In this regard, the literature on this subject reflects a wide variety of interpretation. These substrates can also be labile or their activity can depend on their concentration, which makes them difficult to administer.
The present inventors have thus sought to develop novel compounds which have activity at least on PGHS, and which would then be considered cyclooxygenase activators.
After considerable research, it has now surprisingly and unexpectedly been determined that the 2-amino-4-alkylaminopyrimidine 3-oxides of the invention have the property of activating PGHS.
Furthermore, the presence of an alkyl chain in the 4-position imparts to these compounds improved lipophilic properties.
This reinforces the advantage of these compounds as active agents in the treatment of hair loss.
Accordingly, this invention features novel compounds corresponding to the structural formula (I): 
in which R1 is an alkyl group having from 5 to 20 carbon atoms, and Z is either a hydrogen atom or a radical xe2x88x92OR2, wherein R2 is an alkyl group having from 1 to 12 carbon atoms, as well as the acyl derivatives and acid addition salts thereof.
Consistent herewith, by the term xe2x80x9calkyl radicalxe2x80x9d is intended a linear or branched acyclic radical originating from the removal of a hydrogen atom in a hydrocarbon molecule, such as, for example, a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl or eicosadecyl radical.
In one preferred embodiment of the invention, R1 is an alkyl radical having from 6 to 12 carbon atoms, such as, for example, a hexyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl radicals.
In another preferred embodiment of the invention, R2 is an alkyl radical having from 2 to 6 carbon atoms, such as, for example, an ethyl, propyl, butyl, pentyl or hexyl radical.
Preferred compounds of the invention include:
2-amino-4-pentylaminopyrimidine 3-oxide;
2-amino-4-hexylaminopyrimidine 3-oxide;
2-amino-4-heptylaminopyrimidine 3-oxide;
2-amino-4-octylaminopyrimidine 3-oxide;
2-amino-4-nonylaminopyrimidine 3-oxide;
2-amino-4-decylaminopyrimidine 3-oxide;
2-amino-4-undecylaminopyrimidine 3-oxide;
2-amino-4-dodecylaminopyrimidine 3-oxide;
2-amino-4-tridecylaminopyrimidine 3-oxide;
2-amino-4-tetradecylaminopyrimidine 3-oxide;
2-amino-4-pentadecylaminopyrimidine 3-oxide;
2-amino-4-hexadecylaminopyrimidine 3-oxide;
2-amino-4-heptadecylaminopyrimidine 3-oxide;
2-amino-4-octadecylaminopyrimidine 3-oxide;
2-amino-4-nonadecylaminopyrimidine 3-oxide;
2-amino-4-eicosadecylaminopyrimidine 3-oxide;
2-amino-4-pentylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-octylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-decylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-octylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-decylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-octylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-decylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-decylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-butyloxypyrimidine 3-oxide; and
Even more preferred compounds according to the invention are:
2-amino-4-hexylaminopyrimidine 3-oxide;
2-amino-4-octylaminopyrimidine 3-oxide;
2-amino-4-dodecylaminopyrimidine 3-oxide;
2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide; and yet even more preferred are
2-amino-4-dodecylaminopyrimidine 3-oxide; and 2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide.
This invention also features a process for preparing the 2-amino-4-alkylaminopyrimidine 3-oxides of formula (I).
This process comprises reacting an aliphatic amine with 2-amino-4,6-dichloropyrimidine in a solvent such as ethanol. The compound thus obtained, after purification, is then reacted with a urea/H2O2 complex and phthalic anhydride in a solvent such as isopropanol. After purification, the compound obtained is reacted in the presence of potassium hydroxide and palladium-on-charcoal in a solvent such as absolute ethanol, under a hydrogen pressure in order to provide the corresponding 2-amino-4-alkylaminopyrimidine 3-oxides.
The present invention also features a process for preparing the 2-amino-4-alkylamino-6-alkyloxy-pyrimidine 3-oxides of formula (I).
This process comprises reacting an aliphatic amine with 2-amino-4,6-dichloropyrimidine in a solvent such as ethanol. The compound thus obtained, after purification, is then reacted with a urea/H2O2 complex and phthalic anhydride in a solvent such as isopropanol. After purification, the compound obtained is reacted with an excess of sodium or potassium alkoxide to provide the corresponding 2-amino-4-alkylamino-6-alkyl-oxypyrimidine 3-oxide.
Too, this invention features compositions which comprise at least one compound of the 2-amino-4-alkyl-aminopyrimidine 3-oxides having the structural formula
It will of course be appreciated that the compositions according to the invention can contain the compounds of formula (I) either alone or as mixtures in all proportions.
Too, the xe2x80x9ceffectivexe2x80x9d amount of compound administered corresponds to the amount required to elicit the desired result. One skilled in this art is thus capable of easily evaluating this effective amount, which depends on the nature of the compound used and on the particular individual thus treated.
To provide an order of magnitude, in the compositions according to the invention, the compounds of formula (I) are advantageously present at a concentration ranging from 0.001% to 10% by weight relative to the total weight of the composition and preferably from 0.01% to 2%.
The present invention also features formulating as an active principle, in a physiologically acceptable medium (vehicle, diluent or carrier), into a composition, of an effective amount of at least one compound of formula (I); such compounds/compositions are well suited to induce and/or stimulate hair growth and/or prevent hair loss.
The compositions according to the invention can be ingested, injected or topically applied onto the skin and/or the hair. Depending on the mode of administration, the compositions according to the invention are formulated into any pharmaceutical form normally employed.
For topical application onto the skin or the hair, the composition can be in the form, in particular, of an aqueous or oily solution or a dispersion of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersing a fatty phase in an aqueous phase (O/W) or, conversely, (W/O), or suspensions or emulsions of runny consistency of the cream or aqueous or anhydrous gel type, or alternatively microcapsules or microparticles, or vesicle dispersions of ionic and/or nonionic type. These compositions are formulated via the usual techniques.
They can also be used for the hair in the form of aqueous, alcoholic or aqueous-alcoholic solutions, or in the form of creams, gels, ointments, emulsions or mousses or alternatively in the form of aerosol compositions also comprising a propellant under pressure.
The compositions according to the invention can also constitute a haircare composition, in particular a shampoo, a hairsetting lotion, a treating lotion, a styling cream or gel, a dye composition (in particular an oxidation dye composition) optionally in the form of coloring shampoos, restructuring lotions for the hair, a permanent-waving composition (in particular a composition for the first stage of a permanent-waving operation), a lotion or gel for preventing hair loss, an antiparasitic shampoo, etc.
For systemic injection, the subject compositions can be formulated as an aqueous or oily lotion or in the form of a serum. For the eyes, drops are well suited, and for ingestion, same can be formulated as capsules, granules, syrups or tablets.
The amounts of the various constituents in the compositions according to the invention are those conventional in the fields under consideration.
The compositions according to the invention can also be formulated as solid preparations constituting cleansing soaps or bars.
The subject compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.
When the composition is an emulsion, the proportion of the fatty phase advantageously ranges from 5% to 80% by weight and preferably from 5% to 50% by weight relative to the total weight of the composition. The oils, waxes, emulsifiers and co-emulsifiers included in the composition in emulsion form are chosen from among those that are conventional in the cosmetics field. The emulsifier and the co-emulsifier are advantageously present in the composition in a proportion ranging from 0.3% to 30% by weight, and preferably from 0.5% to 20% by weight, relative to the total weight of the composition. The emulsion can also contain lipid vesicles.
When the composition is an oily solution or gel, the fatty phase can constitute more than 90% of the total weight of the composition.
In known fashion, the subject compositions can also contain additives and adjuvants that are common in the cosmetics field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives and active agents, preservatives, antioxidants, solvents, fragrances, fillers, sunscreening agents, odor absorbers and dyestuffs and colorants. The amounts of these various adjuvants are those conventionally formulated in the cosmetics field, and, for example, range from 0.01% to 10% of the total weight of the composition. Depending on their nature, these additives and adjuvants can be introduced into the fatty phase, into the aqueous phase and/or into the lipid spherules.
Exemplary oils or waxes according to the invention include mineral oils (liquid petroleum jelly), plant oils (liquid fraction of karite butter or sunflower oil), animal oils (perhydrosqualene), synthetic oils (purcellin oil), silicone oils or waxes (cyclomethicone) and fluoro oils (perfluoropolyethers), beeswax, carnauba wax or paraffin wax. Fatty alcohols and fatty acids (stearic acid) can be added to these oils. Exemplary emulsifiers according to the invention include glyceryl stearate, polysorbate-60 and the PEG-6/PEG-32/glycol stearate mixture marketed under the trademark Tefose(copyright)63 by Gattefosse.
Exemplary solvents per this invention include the lower alcohols, in particular ethanol and isopropanol, and propylene glycol.
And exemplary hydrophilic gelling agents include carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxy-propylcellulose, natural gums and clays, and exemplary lipophilic gelling agents include modified clays such as bentones, metal salts of fatty acids, such as aluminum stearates, and hydrophobic silica, ethylcellulose and polyethylene.
The subject compositions can contain other hydrophilic active agents, such as proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.
Lipophilic active agents which are suitable include retinol (vitamin A) and derivatives thereof, tocopherol (vitamin E) and derivatives thereof, essential fatty acids, ceramides, essential oils and salicylic acid and its derivatives.
In one embodiment according to the invention, the subject compositions comprise at least one compound of formula (I) in admixture with other active agents. Among these active agents, particularly representative are:
(1) agents for improving the activity with regard to regrowth of the hair and/or preventing hair loss, and which have already been described for such activity, for example, nicotinic acid esters, including, in particular, tocopheryl nicotinate, benzyl nicotinate and C1-C6 alkyl nicotinates such as methyl or hexyl nicotinates, pyrimidine derivatives, such as 2,4-diamino-6-piperidinopyrimidine 3-oxide or xe2x80x9cMinoxidilxe2x80x9d described in U.S. Pat. Nos. 4,139,619 and 4,596,812, and agents for promoting regrowth of the hair, such as those described in the European patent application published under No. 0,648,488 and assigned to the assignee hereof;
(2) agents which reduce skin differentiation and/or proliferation and/or pigmentation, such as retinoic acid and its isomers, retinol and its esters, vitamin D and derivatives thereof, estrogens such as estradiol, kojic acid or hydroquinone;
(3) antibacterial agents such as clindamycin phosphate, erythromycin or antibiotics of the tetracyclene class;
(4) antiparasitic agents, in particular metronidazole, crotamiton or pyrethroids;
(5) antifungal agents, in particular compounds belonging to the imidazole class, such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allylamine family such as terbinafine, or alternatively octopirox;
(6) antiviral agents such as acyclovir;
(7) steroidal anti-inflammatory agents such as hydrocortisone, betamethasone valerate or clobetasol propionate, or nonsteroidal anti-inflammatory agents such as, for example, ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophen or glycyrrhizic acid;
(8) anaesthetics such as lidocane hydrochloride and derivatives thereof;
(9) anti-pruriginous agents such as thenaldine, trimeprazine or cyproheptadine;
(10) keratolytic agents such as xcex1- and xcex2-hydroxycarboxylic or xcex2-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, salicylic acid, citric acid and fruit acids in general, and 5-n-octanoylsalicylic acid;
(11) anti-free-radical agents such as xcex1-tocopherol or its esters, superoxide dismutases, certain metal-chelating agents or ascorbic acid and its esters;
(12) antiseborrhoeic agents such as progesterone;
(13) antidandruff agents such as octopirox or zinc pyrithione;
(14) antiacne agents such as retinoic acid or benzoyl peroxide;
(15) extracts of plant, marine or bacterial origin.
Other compounds may also be included, for example, Diazoxide, Spiroxazone, phospholipids such as lecithin, linoleic acid, linolenic acid, salicylic acid and derivatives thereof described in FR-2,581,542, e.g., salicylic acid derivatives bearing an alkanoyl group containing from 2 to 12 carbon atoms in the 5-position of the benzene ring, hydroxycarboxylic or ketocarboxylic acids and their esters, lactones and their corresponding salts, anthralin, carotenoids, eicosatetraenoic and eicosatrienoic acids or their esters and amides.
Thus, in one specific embodiment, the compositions according to the invention also comprise at least one active agent or substrate selected from among antibacterial agents, antiparasitic agents, antifungal agents, antiviral agents, anti-inflammatory agents, antipruriginous agents, anaesthetics, keratolytic agents, anti-free-radical agents, antiseborrhoeic agents, antidandruff agents, antiacne agents and/or agents for reducing skin differentiation and/or proliferation and/or pigmentation, and extracts of plant, marine or bacterial origin.
It will also be appreciated that the subject compositions can comprise at least one compound as described above in liposomal form, in particular as described in WO-94/22468, filed Oct. 13, 1994 by Anti Cancer Inc. Thus, the compound encapsulated in the liposomes can be delivered selectively to the hair follicle.
The compositions according to the invention are topically applied onto the alopecic areas of an individual subject""s scalp and hair, and is optionally maintained in contact with such areas for several hours and optionally rinsed therefrom. In one embodiment, a composition containing an effective amount of at least one compound as described above is topically applied during the evening, maintained overnight and optionally shampooed out in the morning. These applications can be repeated daily for one or more months depending on the needs of the individual.
Thus, the present invention also features a cosmetic treatment for the hair and/or the scalp (regime or regimen), comprising topically applying a composition containing an effective amount of at least one compound as described above to the hair and/or the scalp, maintaining this composition in contact with the hair and/or the scalp and optionally rinsing same therefrom.
This treatment has the characteristics of a cosmetic regime/regimen inasmuch as it improves the aesthetics of the hair by providing more vitality and imparting an improved appearance thereto.
The compositions according to the invention are well suited for cosmetic or pharmaceutical applications, in particular dermatological application.